School of Medicine, Western Sydney University, Campbelltown, Australia.
Schizophrenia Research Laboratory, Neuroscience Research Australia, Randwick, Australia; Department of Neuroscience & Physiology, Upstate Medical University, Syracuse, USA; School of Psychiatry, Faculty of Medicine, University of New South Wales, Kensington, Australia.
Behav Brain Res. 2021 May 7;405:113166. doi: 10.1016/j.bbr.2021.113166. Epub 2021 Feb 12.
Handling of laboratory mice affects animal wellbeing and behavioural test outcomes. However, present research has focused on handling effects in common strains of laboratory mice despite the knowledge that environmental factors can modify established phenotypes of genetic mouse models. Thus, we examined the impact of handling on the face validity of a transgenic mouse model for the schizophrenia risk gene neuregulin 1 (i.e. Nrg1 type III overexpression). Nrg1 III tg and wild type-like (WT) control mice of both sexes underwent tail or tunnel handling before being assessed in the open field (OF), elevated plus maze (EPM), social preference/novelty, prepulse inhibition, and fear conditioning tests. Tunnel-handling reduced the startle response in all mice, increased OF locomotion and exploration in males and reduced anxiety in males (OF) and females (EPM) compared to tail-handling. Importantly, tunnel handling induced a more pronounced startle response to increasing startle stimuli in Nrg1 III tg females compared to respective controls, a phenomenon absent in tail-handled females. Finally, Nrg1 III tg males displayed reduced OF exploration and centre locomotion and Nrg1 III tg females displayed increased cue freezing over time compared to controls. In conclusion, handling methods have a significant impact on a variety of behavioural domains thus the impact of routine handling procedures need be considered when testing behavioural phenotypes. Handling did not change the main schizophrenia-relevant characteristics of Nrg1 III tg mice but affected the acoustic startle-response in a genotype- and sex-specific manner. Future research should evaluate the effect of handling on other genetic models.
处理实验小鼠会影响动物的福利和行为测试结果。然而，目前的研究主要集中在常见实验小鼠品系的处理效应上，尽管人们知道环境因素可以改变遗传小鼠模型的既定表型。因此，我们研究了处理对精神分裂症风险基因神经调节蛋白 1（即 Nrg1 型 III 过表达）转基因小鼠模型的行为有效性的影响。雌雄两性的 Nrg1 III tg 和野生型样（WT）对照小鼠在进行旷场（OF）、高架十字迷宫（EPM）、社会偏好/新奇、条件性恐惧和前脉冲抑制测试之前，分别接受尾部或隧道处理。与尾部处理相比，隧道处理减少了所有小鼠的惊跳反应，增加了雄性小鼠的 OF 运动和探索，减少了雄性（OF）和雌性（EPM）的焦虑。重要的是，隧道处理诱导 Nrg1 III tg 雌性对增加的惊跳刺激的惊跳反应比相应的对照更明显，而尾部处理的雌性则没有这种现象。最后，与对照组相比，Nrg1 III tg 雄性小鼠的 OF 探索和中心运动减少，Nrg1 III tg 雌性小鼠随时间的 cue 冻结增加。总之，处理方法对各种行为领域有显著影响，因此在测试行为表型时需要考虑常规处理程序的影响。处理并没有改变 Nrg1 III tg 小鼠的主要精神分裂症相关特征，但以基因型和性别特异性的方式影响了听觉惊跳反应。未来的研究应该评估处理对其他遗传模型的影响。
